INTERACTIONS OF MODIFIED HEMOGLOBINS WITH IRON CHELATORS

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Among the current strategies aimed at decreasing the oxidant effect of HBOCs is the use of iron chelators to prevent the potential molecular and cellular damage caused by iron induced oxygen free radicals. We studies the effects of interactions of desferrioxamine and newly developed pyrone (ethyl maltol) on the rate of autoxidation and hydrogen peroxide mediated oxidation of crosslinked hemoglobins. There was a slight decrease in both the rate of autoxidation and hemichrome formation when ethyl maltol was included in the incubation media of these hemoglobins. Conversely, inclusion of desferrioxamine led to an increase in oxidation products. In the reaction mixture, and in the presence of excess hydrogen peroxide, desferrioxamine led to a 20-30% rise in methemoglobin coupled with slight reduction in the hemichrome formation. Ethyl maltol, on the other hand, had little or no effect. It appears that unlike ethyl maltol, desferrioxamine independent if its iron cheating properties, acts as an oxidizing agent. This may relate to its ability to interact directly with oxygen free radicals resulting in increased methemoglobin formation. Further studies are planned to verify this and to investigate the underlying molecular mechanism of desferrioxamine's action.